Lung fibrosis modeling and compound testing platform using fibrotic lung ECM that recreates the fibrotic disease environment to improve predictiveness and accelerate anti-fibrotic drug development
使用纤维化肺 ECM 的肺纤维化建模和复合测试平台,可重建纤维化疾病环境,以提高预测性并加速抗纤维化药物的开发
基本信息
- 批准号:10793211
- 负责人:
- 金额:$ 10.93万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-01 至 2024-02-28
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAccelerationAnimal ModelAnimalsBasic ScienceBiocompatible MaterialsBiological AssayBiologyBiomanufacturingBiomechanicsBiotechnologyCell Culture TechniquesCellsChronic lung diseaseCoenzyme ACollagenCollagen Type IData SetDecision MakingDependenceDevelopmentDiagnosisDiseaseDisease ProgressionDisease modelDocumentationDrug ModelingsDrug ScreeningEnvironmentEtiologyExperimental ModelsExtracellular MatrixFDA approvedFacility ControlsFibroblastsGelGene ExpressionGenesGoalsHumanHydrogelsIn VitroInternationalInterstitial Lung DiseasesInterventionInterviewInvestigationKnowledgeLegal patentLifeLungLung TransplantationLung diseasesManuscriptsMarketingMechanicsMethodsModelingMultiomic DataOrgan DonorOutputPaperPathogenesisPatient-Focused OutcomesPerformancePersonsPharmaceutical PreparationsPharmacologic SubstancePhasePhenotypePhysiologicalPirfenidonePolystyrenesPredictive ValueProcessProtein SecretionProtocols documentationPublicationsPublishingPulmonary FibrosisPulmonary alveolar structureQuality ControlReportingReproducibilityResearchRespiratory physiologyRisk ReductionSamplingScientistSmall Business Innovation Research GrantSpecific qualifier valueSpecificityStandardizationStructure of parenchyma of lungTechnologyTest ResultTestingTimeTissue ModelTissuesValidationWorkcommercializationcomparativecostdrug developmentdrug discoverydrug testingempowermentfibrotic lunghigh riskhuman tissueidiopathic pulmonary fibrosisimprovedin vitro Modelin vitro testingin vivomanufacturemanufacturing processmetabolomicsmortalitynintedanibnovelnovel therapeuticspredictive modelingproduct developmentquality assuranceresearch and developmentscale upstandard of carestemsuccesssupply chaintechnological innovationtherapeutic developmenttranscriptome sequencingtranscriptomicsvalidation studiesverification and validation
项目摘要
PROJECT ABSTRACT
Xylyx is developing a pulmonary fibrosis disease modeling and anti-fibrotic compound testing platform aimed at
improving the physiological relevance and predictive value of in-vitro models for idiopathic pulmonary fibrosis
(IPF) to power the investigation of IPF disease biology and accelerate development of drugs to treat IPF.
Devastating, intractable, and life-threatening, IPF is an interstitial lung disease characterized by obliteration of
pulmonary alveoli and progressive loss of respiratory function. Over 55,000 new cases of IPF are diagnosed
each year. Median survival is 3–4 years, and annual mortality in the US exceeds 40,000. The etiology and
pathogenesis of IPF remain unknown. Predictive animal and in-vitro models of IPF for basic science research
and drug development are severely lacking, leaving a significant unmet need and market opportunity for a
physiologically-relevant in-vitro platform that enables high-fidelity cell-based phenotypic studies of IPF. This
SBIR Fast Track will support development and validation studies for commercialization of an IPF disease
modeling and compound testing platform that recapitulates in vitro key features of the human IPF disease
environment and has been shown to support fibrotic phenotype of human lung fibroblasts to improve cell-based
assays in early-stage anti-fibrotic drug discovery. The technological innovation is the product’s human IPF fibrotic
lung specificity stemming from proprietary methods for isolating acellular human IPF lung extracellular matrix
(ECM) with the composition and biomechanics of human IPF lung tissue. Our ‘physiomimetic approach’ yields
standardized human fibrotic lung cell culture substrates for predictive in-vitro models of IPF that enable more
physiologic and thus more predictive studies, providing a major competitive advantage over existing products
like collagen-coated polystyrene plates. The goal is validation and commercialization of standard human IPF
lung ECM disease modeling and compound testing platform for predictive in-vitro models of IPF to greatly reduce
dependence on animal models and enable more relevant results for IPF drug developers. Specific aims are to:
(i) determine transcriptomic and metabolomic profiles of lung fibroblasts in human IPF and normal lung ECM
hydrogels, (ii) evaluate quality and consistency of human IPF and normal lung ECM hydrogels, (iii) perform
compound testing studies with IPF standard-of-care drugs. After successful completion of the Fast Track project,
Xylyx will commercialize the IPF compound testing platform to scientists in pharmaceutical companies in need
of predictive IPF disease models for drug discovery and screening, thus reducing the significant costs associated
with late-stage attrition due to poor efficacy, and facilitating the development of improved treatment options for
the more than 3 million sufferers of IPF worldwide. The product of this SBIR Fast Track will immediately enter
the rapidly growing cell culture market segment in biopharma and drug development, valued at USD $6.4B in
2014 and estimated to reach USD $29.2B by 2024, and will support drug development aimed at the USD $3.0B
IPF treatment market.
项目摘要
Xylyx 正在开发肺纤维化疾病建模和抗纤维化化合物测试平台,旨在
提高特发性肺纤维化体外模型的生理相关性和预测价值
(IPF) 推动 IPF 疾病生物学研究并加速治疗 IPF 药物的开发。
IPF 是一种毁灭性、棘手且危及生命的间质性肺疾病,其特征是肺组织消失
肺泡和呼吸功能进行性丧失。诊断出超过 55,000 例 IPF 新病例
每年。美国的中位生存期为 3-4 年,年死亡率超过 40,000 人。病因学和
IPF 的发病机制仍不清楚。用于基础科学研究的 IPF 预测动物和体外模型
和药物开发严重缺乏,留下了巨大的未满足的需求和市场机会
生理相关的体外平台,可实现 IPF 的高保真基于细胞的表型研究。这
SBIR 快速通道将支持 IPF 疾病商业化的开发和验证研究
模拟和复合测试平台,在体外概括人类 IPF 疾病的关键特征
环境,并已被证明支持人肺成纤维细胞的纤维化表型,以改善基于细胞的
早期抗纤维化药物发现中的测定。技术创新是该产品的人体IPF纤维化
肺特异性源于分离无细胞人 IPF 肺细胞外基质的专有方法
(ECM) 与人 IPF 肺组织的组成和生物力学。我们的“拟态方法”产生
用于 IPF 预测体外模型的标准化人纤维化肺细胞培养基质,使更多
生理学研究,因此更具预测性,与现有产品相比具有主要竞争优势
像胶原蛋白涂层的聚苯乙烯板。目标是标准人类 IPF 的验证和商业化
肺 ECM 疾病建模和复合测试平台,用于预测 IPF 体外模型,大大减少
依赖动物模型,为 IPF 药物开发商提供更相关的结果。具体目标是:
(i) 确定人 IPF 和正常肺 ECM 中肺成纤维细胞的转录组学和代谢组学特征
水凝胶,(ii) 评估人 IPF 和正常肺 ECM 水凝胶的质量和一致性,(iii) 执行
IPF 标准治疗药物的化合物测试研究。快速通道项目顺利完成后,
Xylyx将把IPF化合物测试平台商业化给有需要的制药公司的科学家
用于药物发现和筛选的预测性 IPF 疾病模型,从而降低相关成本
由于疗效不佳而导致晚期自然减员,并促进开发改进的治疗方案
全球有超过 300 万 IPF 患者。本次SBIR快速通道的产品将立即进入
生物制药和药物开发领域快速增长的细胞培养市场,价值 USD $6.4B
2014 年预计到 2024 年将达到 USD $29.2B,并将支持目标为 USD $3.0B 的药物开发
IPF治疗市场。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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John David O'Neill其他文献
John David O'Neill的其他文献
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{{ truncateString('John David O'Neill', 18)}}的其他基金
Lung fibrosis modeling and compound testing platform using fibrotic lung ECM that recreates the fibrotic disease environment to improve predictiveness and accelerate anti-fibrotic drug development
使用纤维化肺 ECM 的肺纤维化建模和复合测试平台,可重建纤维化疾病环境,以提高预测性并加速抗纤维化药物的开发
- 批准号:
10515017 - 财政年份:2021
- 资助金额:
$ 10.93万 - 项目类别:
Lung fibrosis modeling and compound testing platform using fibrotic lung ECM that recreates the fibrotic disease environment to improve predictiveness and accelerate anti-fibrotic drug development
使用纤维化肺 ECM 的肺纤维化建模和复合测试平台,可重建纤维化疾病环境,以提高预测性并加速抗纤维化药物的开发
- 批准号:
10660437 - 财政年份:2021
- 资助金额:
$ 10.93万 - 项目类别:
Lung fibrosis modeling and compound testing platform using fibrotic lung ECM that recreates the fibrotic disease environment to improve predictiveness and accelerate anti-fibrotic drug development
使用纤维化肺 ECM 的肺纤维化建模和复合测试平台,可重建纤维化疾病环境,以提高预测性并加速抗纤维化药物的开发
- 批准号:
10609532 - 财政年份:2021
- 资助金额:
$ 10.93万 - 项目类别:
Lung fibrosis modeling and compound testing platform using fibrotic lung ECM that recreates the fibrotic disease environment to improve predictiveness and accelerate anti-fibrotic drug development
使用纤维化肺 ECM 的肺纤维化建模和复合测试平台,可重建纤维化疾病环境,以提高预测性并加速抗纤维化药物的开发
- 批准号:
10323494 - 财政年份:2021
- 资助金额:
$ 10.93万 - 项目类别:
Biomimetic lung sealant to rapidly heal pulmonary air leaks, decrease recovery time, and reduce associated costs to the healthcare system,
仿生肺密封剂可快速治愈肺部漏气、缩短恢复时间并降低医疗保健系统的相关成本,
- 批准号:
10005701 - 财政年份:2020
- 资助金额:
$ 10.93万 - 项目类别:
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